This proposal requests funds for the acquisition of two mass spectrometers, the Perseptive DE STR and the Finnigan LC-Q instruments, plus the nanoelectrospray ionization source for both the Finnigan LC-Q and the existing Sciex API-III mass spectrometers, for the analysis of biological molecules for research programs at the Albert Einstein College of Medicine. The instruments will be used within the context of an established, productive resource laboratory with documented experience in interfacing mass spectrometry to basic biomedical research projects and in interacting with diverse groups of investigators. The rationale for assembling the suite of mass spectrometry instruments, including those requested in this proposal, is the need for higher mass accuracies and sensitivities for present and future projects, the number and complexity of established and developing projects, and the mass spectrometry experience of the personnel. Major projects address important issues in signal transduction, protein processing and sorting, immunology, mechanistic enzymology, protein structure-function analysis, and analysis of nucleic acids. We wish to address the advanced analytical needs of existing research programs and the challenging questions in experimental biology now being developed.